Hepatic Effects of Estrogen on Plasma Distribution of Small Dense Low-Density Lipoprotein and Free Radical Production in Postmenopausal Women

Abstract

Aim: Hepatic effects of estrogen therapy on low-density lipoprotein (LDL) subfraction or oxidative stress have not been previously evaluated. The purpose of the present study was to investigate whether the differential hepatic effects of estrogen affect plasma distribution of small dense LDL and free radical production in postmenopausal women.

Methods: In all, 45 postmenopausal women were given 0.625 mg/day of oral conjugated equine estrogen (CEE) (n=15), 1.0 mg/day of oral 17β estradiol (E2) (n=15), or 50 μg/day of transdermal 17βE2 (n=15) for 3 months. Subjects received either estrogen alone or with dydrogesterone at 5 mg/day. Plasma concentrations of sex hormone-binding globulin (SHBG), lipids, metallic ions, and derivatives of reactive oxygen metabolites (d-ROMs) were measured.

Results: CEE, but not oral 17βE2, increased the plasma concentrations of triglyceride, copper (Cu), and d-ROMs and the ratio of small dense LDL/total LDL cholesterol, a marker for plasma distribution of small dense LDL. Transdermal 17βE2 decreased d-ROMs concentrations but did not significantly change other parameters. Plasma concentrations of SHBG increased in the 3 groups. Estrogen-induced changes in triglyceride correlated positively either with changes in SHBG (R=0.52, P=0.0002) or the ratio of small dense LDL/total LDL cholesterol (R=0.65, P＜0.0001). Changes in Cu also correlated positively either with changes in SHBG (R=0.85, P＜0.0001) or d-ROMs (R=0.86, P＜0.0001).

Conclusion: The hepatic effects of different routes or types of estrogen therapy may be associated with plasma distribution of small dense LDL and free radical production in postmenopausal women.

Fig. 1.

(A) Relationship between changes in plasma triglyceride and sex hormone-binding globulin. Triangles indicate conjugated equine estrogen group, squares indicate oral 17β estradiol (E₂) group, and circles indicate transdermal 17βE₂ group. (B) Relationship between changes in plasma triglyceride and small dense LDL/LDL ratio.

Fig. 2.

(A) Relationship between changes in plasma copper and sex hormone-binding globulin. Triangles indicate conjugated equine estrogen group, squares indicate oral 17β estradiol (E₂) group, and circles indicate transdermal 17βE₂ group. (B) Relationship between changes in plasma copper and derivatives of reactive oxygen metabolites.